Cell migration plays a central role in embryonic development, wound healing, inflammation and tumor metastasis. This proposal focuses on alpha4beta1 integrin, which is expressed in many cell types that migrate directionally in vivo and can confer motility on cells in culture. Our main goal is to understand the mechanism by which alpha4beta1 promotes cell migration. We propose that phosphorylation at the cytoplasmic tail of alpha4 plays a regulatory role in alpha4-promoted cell migration. To test this hypothesis, we will (1) determine the effects of phosphorylation at the cytoplasmic tail of alpha4 in migratory behavior of cells; (2) determine how phosphorylation regulates alpha4beta1-promoted cell migration; and (3) identify proteins that interact with phosphorylated alpha4 tail. These studies will provide unique insight into the signaling mechanism by which alph4beta1-promoted cell migration is regulated and will increase our understanding on the role of integrin-mediated molecular interactions in the development of metastatic tumors.